Allosteric Small-Molecule Serine/Threonine Kinase Inhibitors.
Allosteric Small-Molecule Serine/Threonine Kinase Inhibitors. Adv Exp Med Biol. 2019;1163:253-278 Authors: Panicker RC, Chattopadhaya S, Coyne AG, Srinivasan R Abstract Deregulation of protein kinase activity has been linked to many diseases ranging from cancer to AIDS and neurodegenerative diseases. Not surprisingly, drugging the human kinome - the complete set of kinases encoded by the human genome - has been one of the major drug discovery pipelines. Majority of the approved clinical kinase inhibitors target the ATP binding site of kinases. However, the remarkable sequence and structural similarity of ATP binding pockets of kinases make selective inhibition of kinases a daunting task. To circumvent these issues, allosteric inhibitors that target sites other than the orthosteric ATP binding pocket have been developed. The structural diversity of the allosteric sites allows these inhibitors to have higher selectivity, lower toxicity and improved physiochemical properties and overcome drug resistance associated with the use of conventional kinase inhibitors. In this chapter, we will focus on the allosteric inhibitors of selected serine/threonine kinases, outline the benefits of using these inhibitors and discuss the challenges and future opportunities. PMID: 31707707 [PubMed - in process]
Conclusions There was variable uptake of the PtDAs between the cases. Men who received the PtDA had positive outcomes. Several strategies were identified to increase or sustain PtDA use. Implications for Practice Nurses have a key role in supporting men making decisions about prostate cancer treatment by providing PtDAs, answering questions, and advocating for men's preferences.
CONCLUSIONS AND SIGNIFICANCE: Data suggest that tumor tissue expression of hnRNP M and/or of HSP 90α deserve further investigation and clinical validation as potential novel risk stratification aids in patients with stage I-II cutaneous head and neck malignant melanoma. PMID: 31803364 [PubMed]
[Daily Maverick] In the shadow of HIV many things are hidden. Do a quick Google search ('in the shadow of HIV') and a torrent of disease and social ills will blast across your browser. You'll find gender-based violence and stigma, sugar-daddies, obesity and hypertension, patriarchy, cancer and diabetes, denial, guilt, and the opioid crisis. Also hiding, deep in the shadows, are adolescent boys and young men.
Cancer immunotherapies that engage immune cells to fight against tumors are proving to be powerful weapons in combating cancer and are becoming increasingly utilized in the clinics. However, for the majority o...
This article aims to provide healthcare professionals with the knowledge to identify potentially malignant disorders and to aid them in biopsy site identification.
Researchers are touting the efficacy of a new, incision-free MRI-guided procedure...Read more on AuntMinnie.comRelated Reading: MRI restaging for recurrent prostate cancer has its flaws Prostate cancer patients prefer mpMRI over biopsy Which biopsy method best detects prostate cancer? AIUM: TRUS or MRI for prostate diagnosis? Multiparametric MRI aids in prostate cancer follow-up
Although the Kaposi sarcoma (KS) is one of the AIDS defining entity and seen in almost one third of HIV infected patients with low CD4 cell counts, it is not uncommon in HIV seronegative persons, but genital K...
Whasun Lim In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that can...
CONCLUSIONS: Urinary PCA3 has an acceptable diagnostic accuracy, aids in the study of patients with suspected prostate cancer, and can be used as a guide for directing the performance of the first prostate biopsy and decreasing unnecessary biopsies. PMID: 31793864 [PubMed - as supplied by publisher]